Fabrication Of Peptides Mediated Nanoparticles As Drug Delivery System

Targeted nano-drug delivery system is an effective method for cancer treatment,which can target cancer tissues without affecting normal tissues.The targeted nano-drug delivery system can slowly release drugs to cure cancer under microenvironment stimulus in cancer tissue.In this study,we fabricated two kinds of peptide-mediated drug carrier: peptide-guided dual-sensitive prodrug micelle（MPPM）and peptide-guided mesoporous silica nanoparticle.The specific content is as follows:（1）Peptide-mediated dual-sensitive prodrug micelle.The prodrug micelle is formed in water by self-assembly of amphiphilic molecules,which composed of hydrophobic anti-cancerand amphiphilic peptide linking via disufide bond.Peptide-guided dual-sensitive prodrug micelle was obtained after2,3-dimethylmaleic anhydride decorating.Due to cleavage of unsaturated bondα-amino-β-carboxyl on the polypeptide side chain under the stimulation of mild acidic environment,the negative surface charge of prodrug micelle transformed to positive.The prodrug micelle was efficiently uptaken by cancerous cells mediated by cell penetrating peptides-K₁₀（Poly（lys）10）on the outer layer of the micelle.Thereafter,anti-cancer drug doxorubicin（DOX）was released induced by concentrated glutathione（GSH）inside cancerous cells;meanwhile,the structure of prodrug micelles could be loosened due to degradation by proteases,which could accelerate drug diffusion and drug release.（2）Peptide-mediated mesoporous silica nanoparticle（MSN）.The drug carrier was dual pH-responsive and can target cancerous cells followed by precisely controlled drug release.Firstly,we synthesize sulphydryl mesoporous silica（MSN-SH）and zwitterionic silicon alkylation reagents modified zinc oxide（ZnO-ZWS）.Due to chelation between thiol（SH）and Zn2+,DOX loaded MSN can be capped by ZnO-ZWS to obtain ZnO@MSN.Then,ZnO@MSN was functionalized with thiolmodified cell penetrating peptide（Peptide）to obtain Peptide@Zn O@MSN.After DMA modifying,the drug carrier Peptide（DMA）@Zn O@MSN was obtained.The drug carrier can accumulated at cancer tissue by though charge-reversal of the peptide on the outer layer of drug carrier.Under mild acidic environment stimulus in cancer tissue,acid sensitive bond α-amino-β-carboxyl unsaturated would cleaved and the surface charge of drug carrier transforms from negative to positive.Then drug carriers could uptaken by cancer cell efficiently.Thereafter,DOX could be released induced by low pH inside cancerous cell by dissolving of ZnO.